Aldehyde dehydrogenase (ALDH); c-Met proto-oncogene (MET; HGFR); epidermal growth factor receptor 1 (EGFR1; HER1; ErbB1)

Cell culture and mouse studies suggest ALDH inhibitors could help treat cancer. In human cancer cell lines expressing MET or EGFR1, the acquisition of resistance to inhibitors was associated with upregulation of ALDH. In multiple kinase-dependent cancer cell lines, an ALDH inhibitor plus an inhibitor of the respective kinase increased cell death compared with either agent alone. In mice bearing EGFR1-dependent xenograft lung tumors, an ALDH inhibitor plus an EGFR1 inhibitor decreased tumor growth and increased time to tumor recurrence compared with an EGFR1 inhibitor alone. Ongoing work includes testing ALDH inhibitors in mouse models of other cancers.
Tekmira Pharmaceuticals Corp. has TKM-ALDH2, an siRNA targeting aldehyde dehydrogenase 2 family mitochondrial (ALDH2) formulated using lipid nanoparticle delivery technology, in preclinical testing to treat addiction.

SciBX 7(24); doi:10.1038/scibx.2014.699
Published online June 19, 2014

Patent and licensing status undisclosed

Raha, D. et al. Cancer Res.;
published online May 8, 2014;
Contact: Jeff Settleman, Genentech Inc.,
San Francisco, Calif.